§ 158.740 - Microbial pesticides—Product analysis data requirements.

(a) Microbial pesticides product analysis data requirements—(1) Table. Sections 158.50 and 158.100 through 158.102 describe how to use this table to determine the microbial pesticides—product analysis data requirements and the substance to be tested.

Kind of data required(2) NotesGeneral use patternsTerrestrialFood cropNonfoodAquaticFood cropNonfoodGreenhouseFood cropNonfoodForestryDomestic outdoorIndoorTest substanceData to support MPData to support EPGuidelines reference No.Product identity manufacturing process[R][R][R][R][R][R][R][R][R]MPEP*151-20(i)[R][R][R][R][R][R][R][R][R]MP and TGAIEP* and TGAI151-21Discussion of formation of unintentional ingredients(ii)[R][R][R][R][R][R][R][R][R]MP and TGAIEP* and TGAI151-22Analysis of samples(iii)[CR][CR][CR][CR][CR][CR][CR][CR][CR]MP and TGAIEP* and TGAI151-23Certification of limits[R]R[R]R[R]RRRRMPEP*151-25Analytical methodsRRRRRRRRRMPEP*151-25Physical and chemical properties[R][R][R][R][R][R][R][R][R]MP and TGAIEP* and TGAI151-26Submittal of samples(iv)[CR][CR][CR][CR][CR][CR][CR][CR][CR]MP and TGAI, PAIEP* TGAI and PAI151-27Key: R=Required; CR=Conditionally required; MP=Manufacturing-use product: EP*=End-use product (asterisk identifies those data requirements that end-use applicants (i.e., “formulators”) must satisfy, provided that their active ingredient(s) is (are) purchased from a registered source); TGAI=Technical grade of the active ingredient;[]=Brackets (i.e., [R], [CR]) indicate data requirements that apply when an experimental use permit is being sought.(2) Notes. The following notes are referenced in column two of the table contained in paragraph (a)(1) of this section.(i) If an experimental use permit is being sought, a schematic diagram and/or description of the manufacturing process will suffice if the pesticide is not already under scale production.(ii) If the product is not already under full scale production and an experimental use permit is being sought, a discussion of unintentional ingredients shall be submitted to the extent this information is available.(iii) Required to support registration of each manufacturing-use product and end use products produced by an integrated formulation system. Data on other end use products will be required on a case-by-case basis. For pesticide in the production stage, a rudimentary product analytical method and data will suffice to support an experimental use permit. AAA(iv) Routinely required for products produced by an integrated formulation system. Required on a case-by-case basis for other products or materials.

(b) Microbial pesticides-residue data requirements—(1) Table. Sections 158.50 and 158.100 through 158.102 describe how to use this table to determine the microbial pesticides-residue data requirements and the substances to be tested.

Kind of data required(2) NotesGeneral use patternsTerrestrialFood cropNonfoodAquaticFood cropNonfoodGreenhouseFood cropNonfoodForestryDomestic outdoorIndoorTest substanceData to support MPData to support EPGuidelines reference No.Residue data(i)[CR][CR][CR][CR][CR][CR][CR][CR][CR]153-4Key: CR=Conditionally required data; EP=End-use product; MP=Manufacturing-use product; []=Brackets (i.e., [CR]) indicate data requirements that apply when an experimental use permit is being sought.(2) Notes. The following notes are referenced in column two of the table contained in paragraph (b)(1) of this section.(i) Residue data requirements shall apply to microbial pesticides when Tier II or Tier III toxicology data are required, as specified for microbial pesticides in (c)(1) of this section.(ii) [Reserved)

(c) Microbial pesticides-toxicology data requirements—(1) Table. Sections 158.50 and 158.100 through 158.102 describe how to use this table to determine the microbial pesticides-toxicology data requirements and the substances to be tested.

Kind of data required(2) NotesGeneral use patternsTerrestrialFood cropNonfoodAquaticFood cropNonfoodGreenhouseFood cropNonfoodForestryDomestic outdoorIndoor useTest substanceData to support MPData to support EPGuidelines reference No.Tier I:Acute oral[R][R][R][R][R][R][R][R][R]MP and TGAIEP* or EP* dilution and TGAI152-30Acute dermal[R][R][R][R][R][R][R][R][R]MP and TGAIEP* or EP dilution and TGAI152-31Acute inhalation(i)[R][R][R][R][R][R][R][R][R]MP and TGAIEP* or EP Dilution* and TGAI152-32I.V., I.C., I.P. injection(ii)[R][R][R][R][R][R][R][R][R]TGAITGAI152-33Primary dermal[R][R][R][R][R][R][R][R][R]MPEP*152-34Primary eye[R][R][R][R][R][R][R][R][R]MPEP*152-35Hypersensitivity study(iii)RRRRRRRRRMPEP*152-36Hypersensitivity incidents(iv)CRCRCRCRCRCRCRCRCR152-37Immune response[R]R[R]R[R]RRRRTGAITGAI152-38Tissue culture(v)[R]R[R]R[R]RRRRTGAITGAI152-39Tier II:Acute oral(vi)CRCRCRCRCRCRCRCRCRMPEP*152-40Acute inhalation(vii)CRCRCRCRCRCRCRCRCRMPEP*152-41Subchronic oral(viii)CRCRCRCRCRCRCRCRCRTGAITGAI152-42Acute I.P., I.C.(ix)CRCRCRCRCRCRCRCRCRTGAITGAI152-43Primary dermal(x)CRCRCRCRCRCRCRCRCREP*152-44Primary eye(xi)CRCRCRCRCRCRCRCRCREP*152-45Immune response(xii)CRCRCRCRCRCRCRCRCRTGAITGAI152-46Teratogenicity(xiii)CRCRCRCRCRCRCRCRCRTGAITGAI152-47Virulence enhancement(xiv)CRCRCRCRCRCRCRCRCRTGAITGAI152-48Mammalian mutagenicity(xv)CRCRCRCRCRCRCRCRCRTGAITGAI152-49Tier III:Chronic feeding(xvi)CRCRCRCRTGAITGAI152-50Oncogenicity(xvii)CRCRCRCRTGAITGAI151-51Mutagenicity(xviii)CRCRCRCRCRCRCRCRCRTGAITGAI152-52Teratogenicity(xix)CRCRCRCRCRCRCRCRCRTGAITGAI152-53Key: R=Required; CR=Conditionally required; MP=Manufacturing-use product; EP*=End use product (asterisk identifies those data requirements that end-use applicants (i.e., “formulators”) must satisfy, provided that their active ingredient(s) is (are) purchased from a registered source); TGAI=Technical Grade of the Active Ingredient; []=Brackets (i.e., [R], [CR]) indicate data requirements that apply when an experimental use permit is being sought.(2) Notes. The following notes are referenced in column two of the table contained in paragraph (c)(1) of this section.(i) Required if 20 percent or more of the aerodynamic equivalent of the product (as registered or under conditions of use) is composed of particulates less than 10 microns in diameter.(ii) Data required for products as follows:(A) Intravenous (“IV”) infectivity study for bacterial, and viral agents;(B) Intracerebral (“IC”) infectivity study for viral and protozoan agents; and(C) Intraperitoneal (“IP”) infectivity study for fungal and protozoan agents.(iii) Required if commonly recognized use practices will result in repeated human contact by inhalation or dermal routes.(iv) Hypersensitivity incidents must be reported, if they occur.(v) Data required for products whose active ingredient is a virus.(vi) Required if survival, replication, infectivity, toxicity, or persistence of the microbial agent (virus or protozoa) is observed in the test animals treated in the Tier I acute oral infectivity tests or the intraperitoneal or intracerebral injection test for protozoa.(vii) Required if survival, replication, infectivity, toxicity, or persistence of the microbial agent (virus or protozoa) is observed in the test animals treated in the comparable Tier I acute inhalation tests.(viii) Required if there is evidence of survival, replication, infectivity, or persistence of the protozoan agent in the Tier I oral infectivity test.(ix) Required if in Tier I acute oral infectivity testing, Tier I dermal toxicity/infectivity testing, or Tier I intraperitoneal or intracerebral injection testing, the test microorganism (bacteria, fungi, or protozoa) survived for more than 2 weeks, caused toxic effects, or caused a severe illness response in an experimental animal as evidenced by irreversible gross pathology, severe weight loss, toxemia, or death.(x) Required if infectivity or if marked edema or broad erythema was observed in the Tier I dermal irritation study.(xi) Required if infectivity or if severe ocular lesions are observed in the Tier I primary eye irritation study.(xii) Required if results of the Tier I immune response test indicate abnormalities.(xiii) Required when Tier I tests on viral agents show replication of the virus in mammalian hosts and significant damage to mammalian cells.(xiv) Required when Tier I infectivity tests on bacteria or fungi indicate prolonged survival (including presence of viable microbial agents in test animal excreta) and/or multiplication (infectivity) of the bacteria or fungal agent, respectively.(xv) Required if any of the following criteria are met:(A) Acute infectivity tests are positive in Tier I studies.(B) Adverse effects are observed in immune response studies.(C) Positive results are obtained in tissue culture tests with viral agents.(xvi) Required when the potential for chronic adverse effects (e.g., replication or persistence of viral or subviral constituents, protozoans, fungi, or bacteria) are demonstrated by any of the Tier II tests (except primary dermal, primary ocular, and mammalian mutagenicity tests).(xvii) Required when the potential for oncogenic effects is indicated (e.g., adverse cellular effects due to presence, replication, or persistence of viral or subviral constituents, or bacteria, fungi or protozoans; or mutagenic effects) by any of the Tier II tests except the primary dermal and primary ocular studies.(xviii) Required when the potential for mutagenic effects is indicated (e.g., adverse cellular effects due to presence, replication, or persistence of viral or subviral constituents, bacteria, fungi or protozoa) by any of the Tier II tests except primary dermal or primary ocular studies.(xix) Required when the potential for teratogenic effects is expected based on the presence of persistence of fungi, bacteria, viruses, or protozoa in mammalian species as a result of testing performed in Tier II, except primary dermal and primary ocular studies.

(d) Microbial pesticides non-target organism and environmental expression data requirements—(1) Table. Sections 158.50 and 158.100 through 158.102 describe how to use this table to determine the microbial pesticides non-target organism and environmental expression data requirements and substances to be tested.

Kind of data required(2) NotesGeneral use patternsTerrestrialFood cropNonfoodAquaticFood cropNonfoodGreenhouseFood cropNonfoodForestryDomestic outdoorIndoor useTest substanceData to support MPData to support EPGuidelines reference No.Tier I:Avian oral(i), (ii), (iii)[R][R][R][R]CRCR[R][R]CRTGAITGAI154-16Avian injection test(i), (ii), (iii)[R][R][R][R]CRCR[R][R]CRTGAITGAI154-17Wild mammal testing(iv)CRCRCRCRCRCRTGAITGAI154-18Freshwater fish testing(i)[R][R][R][R]CRCR[R]CRCRTGAITGAI154-19Freshwater aquatic invertebrate testing(i)[R][R][R][R]CRCR[R]CRCRTGAITGAI154-20Estuarine and marine animal testing(v)CRCRCRCRCRCRTGAITGAI154-2Nontarget plant studies[R][R][R][R][R][R]CRTEPTEP154-2Nontarget insect testing[R][R][R][R]CRCR[R][R]TGAITGAI154-23Honey bee testing[R][R][R][R]CRCR[R][R]TGAITGAI154-24Tier II:Terrestrial environmental testing(vi)CRCRCRCRCRCRTGAI or TEPTGAI or TEP155-18Freshwater environmental expression tests(vii)CRCRCRCRCRCRTGAI or TEPTGAI or TEP155-19Marine or estuarine environmental expression tests(xiii), (ix)CRCRCRCRCRCRTGAI or TEPTGAI or TEP155-20Tier III:Terrestrial wildlife and aquatic organism testing(x)CRCRCRCRCRCRTGAI or TEPTGAI or TEP154-25Avian pathogenicity/reproduction test(xi)CRCRCRCRCRCRTGAITGAI154-26Definitive aquatic animal tests(xii)CRCRCRCRCRCRTGAITGAI154-27Aquatic embryo larvae and life cycle studies(xiii)CRCRCRCRCRCRTGAITGAI154-28Aquatic ecosystem test(xiv)CRCRCRCRCRCRTGAITGAI154-29Special aquatic tests (reserved)154-30Nontarget plant studies(xv)CRCRCRCRCRCRTGAITEP154-31Tier IV:(xvi)Simulated and actual field tests (birds, mammals)(xiii)CRCRCRCRCRCRTEPTEP154-33Simulated and actual field tests (aquatic organisms)(xvii), (xviii)CRCRCRCRCRCRTEPTEP154-34Simulated and actual field tests (insect predators, parasites) (reserved)154-35Simulated and actual field tests (insect pollinators) (reserved)154-36 AAAKey: R=Required; CR=Conditionally required; []=Brackets (i.e., [R], [CR]) indicates data requirements that apply to products for which an experimental use permit is being sought; MP=Manufacturing-use Product; TEP=Typical end-use product; TGAI=Technical grade of the active ingredient; EP=End-use product; PAI=“Pure” active ingredient. AAA(2) Notes. The following notes are referenced in column two of the table contained in paragraph (d)(1) of this section. AAA(i) Tests for pesticides intended solely for indoor application will be required on a case-by-case basis, depending on use pattern, production volume, and other pertinent factors. AAA(ii) Preferable test species are: bobwhite quail or mallard for avian acute oral and avian dietary studies; rainbow trout for freshwater fish studies. AAA(iii) Data from either the avian acute oral or the avian injection study are required to support an experimental use permit. AAA(iv) Required on a case-by-case basis if results of tests required by paragraph (c)(1) of this section are inadequate or inappropriate for assessment of hazards to wild animals. AAA(v) Required when product is intended for direct application into the estuarine or marine environment or expected to enter this environment in significant concentrations because of expected use or mobility pattern. AAA(vi) Required when toxic or pathogenic effects are observed in any of the following Tier I tests for microbial pest control agents: AAA(A) Avian single dose oral toxicity and pathogenicity tests. AAA(B) Avian injection pathogenicity tests. AAA(C) Wild mammals toxicity and pathogenicity test. AAA(D) Plant studies—terrestrial. AAA(E) Honey bee toxicity/pathogenicity test. AAA(F) Testing for toxicity/pathogenicity to insect predators and parasites. AAA(vii) Required when toxic or pathogenic effects are observed in any of the following Tier I test for microbial pest control agents: AAA(A) Freshwater fish toxicity and pathogenicity testing. AAA(B) Freshwater aquatic invertebrate toxicity and pathogenicity test. AAA(C) Plant studies—aquatic. AAA(viii) Required if product is applied on land or in fresh water and toxic or pathogenic effects are observed in any of the following Tier I tests for microbial pest control agents: AAA(A) Estuarine and marine animal toxicity and pathogenicity test. AAA(B) Plant studies—estuarine or marine. AAA(ix) Required if product is applied in marine or estuarine environments and toxic or pathogenic effects are observed in any of the following Tier I tests: AAA(A) Avian single dose oral toxicity and pathogenicity test. AAA(B) Avian injection pathogenicity test. AAA(C) Estuarine and marine animal toxicity and pathogenicity test. AAA(x) Required when toxic effects on nontarget terrestrial wildlife or aquatic organisms are reported in one or more Tier I tests and results of Tier II tests indicate exposure of the mocrobial agent to the affected nontarget terrestrial wildlife or aquatic organisms. AAA(xi) Required when: AAA(A) Pathogenic effects are observed in Tier I avian tests at a level equal to the adjusted host equivalent amount. AAA(B) Chronic, carcinogenic, or teratogenic effects are reported in tests required by paragraph (c)(1) of this section for evaluating hazard to humans and domestic animals. AAA(C) Tier II Environmental expression testing indicates that exposure of terrestrial animals to the microbial agent is likely. AAA(xii) Required when product is intended for use in water or expected to be transported to water from the intended use site, and when pathogenicity or infectivity was observed in Tier I tests. AAA(xiii) Required when both of the following conditions are met: AAA(A) Pathogenic effects at actual or expected field residue exposure levels are reported in Tier III. AAA(B) The agency determines that quarantine methods will prevent the microbial pest control agent from contaminating areas adjacent to the test area. AAA(xiv) Required if, after an analysis of the microbial agent's properties, the individual use patterns, and the results of previous nontarget organism and environmental expression tests, it is determined that use of the microbial agent may result in adverse effects on the nontarget organisms in aquatic environments, including those of the water column and bottom sediments. When a microbial pest control agent is used in or is expected to transport to water from the intended use site, major considerations for requiring these infectivity tests include, but are not limited to: AAA(A) Infectivity or pathogenicity demonstrated in previous testing. AAA(B) Viability of the microorganism in natural waters as demonstrated in Tier II tests. AAA(xv) Required if the product is transported from the site of application by air, soil, or water or transmission by other animals. The extent of movement will be determined by the environmental expression tests in Tier II. AAA(xvi) The Agency expects that Tier IV requirements would be imposed retrospectively—after product registration as post registration monitoring, since it is unlikely a registrant would pursue registration of a microbial agent posing potential hazards such that testing beyond Tier III is required. AAA(xvii) Short term simulated or actual field studies are required when it is determined that the product is likely to cause adverse short-term or acute effects, based on consideration of available laboratory data, use patterns, and exposure rates. AAA(xviii) Data from a long-term simulated field test (e.g., where reproduction and growth of confined populations are observed) and/or an actual field test (e.g., where reproduction and growth of natural populations are observed) are required if laboratory data indicate adverse long-term, cumulative, or life-cycle effects may result from intended use.